Catalysts for nucleophilic substitution, systhesis thereof, composition containing them and use thereof

ABSTRACT

The invention concerns novel catalysts for aromatic nucleophilic substitution. Said catalysts are compounds of the general formula (I), wherein: R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 , identical or different, are selected among hydrocarbon radicals; the Pn&#39;s, advantageously the same, are selected among metalloid elements of column V of a period higher than nitrogen; Z is a metalloid element of column V, advantageously distinct from Pn; preferably a nitrogen (N, P, As, Sb). The invention is applicable to organic synthesis.

[0001] The present invention relates to a novel method for performingnucleophilic substitutions, especially of SN_(Ar) type, and is moreparticularly directed toward novel catalysts. Although the effect isless pronounced, it is also directed toward the use of these catalystsfor SN₂ reactions.

[0002] The invention is more particularly of interest to aromaticnucleophilic substitution reactions involving the following reactionscheme:

[0003] attack of a nucleophilic agent on an aromatic substrate withcreation of a bond between said nucleophilic agent and said substrate,on a carbon bearing a leaving group, so as to form an intermediatecompound known as a Meisenheimer intermediate (when the nucleophile isan anion) or equivalent, and then

[0004] loss of said leaving group.

Example of a Meisenheimer Example of an intermediate intermediate withequivalent to the optional radical R Meisenheimer intermediate n    thenumber of substituents with optional radical R EWG Electron-WithdrawingGroup EWG Electron-Withdrawing Group Nu  anionic nucleophile Nu  neutralnucleophile

[0005] Examples of SN_(Ar) intermediates will be given below:

[0006] Reactions of this type are particularly advantageous forobtaining halogenated aromatic derivatives and are especially used toperform exchanges between fluorine, on the one hand, and halogen(s) of ahigher row or pseudohalogen on an aromatic substrate.

[0007] The leaving group may thus be a nitro group, advantageously apseudohalogen, or, preferably, a halogen atom, especially having anatomic number higher than that of fluorine.

[0008] The term “pseudohalogen” is intended to denote a group which, onleaving, leads to an oxygenated anion, the anionic charge being borne bythe chalcogen atom and the acidity of which is at least equal to that ofacetic acid, advantageously to the second acidity of sulfuric acid, andpreferably to that of trifluoroacetic acid. In order to determine theposition on the acidity scale, reference should be made to the pKavalues for the average to strong acidities from carboxylic acids up toacetic acid and to determine the position on the scale of Hammettconstants (see FIG. 1) starting from trifluoroacetic acid.

[0009] As illustrations of pseudohalogens of this type, mention may bemade in particular of sulfinic and sulfonic acids, which areperhalogenated on the carbon bearing sulfur, and also carboxylic acidsperfluorinated α to the carboxylic function.

[0010] When the leaving group is a nitro group, this group is generallyreplaced with a chlorine or fluorine atom. However, most of thesereagents make it necessary to work at very high temperatures and themechanism is not always found to be a nucleophilic substitution.Moreover, loss of the nitro group leads to the formation of oxygenatedand halogenated nitrogen derivatives that are particularly aggressivewith regard to the substrate, or even explosive.

[0011] As regards the variant involving the substitution of a halogenatom present on an aromatic nucleus with another halogen atom, thisgenerally requires at least a partial deactivation of said nucleus. Tothis end, the aryl radical to be converted is preferably electron-poorand has an electron density at most equal to that of benzene, and atmost in the region of that of a chlorobenzene, preferably adichlorobenzene.

[0012] This depletion may be due to the presence in the aromatic ring(six-membered) of a hetero atom, for instance in pyridine or quinoline(the depletion in this case involves a six-membered ring). In thisparticular case, the depletion is large enough for the substitutionreaction to take place very easily and does not require any particularassociated activation. The electron-poor state may also be induced withelectron-withdrawing substituents present on this aromatic ring. Thesesubstituents are preferably chosen from groups that withdraw via aninductive effect or via a mesomeric effect as defined in the referenceorganic chemistry book “Advanced Organic Chemistry” by J. March, 3rdedition, published by Willey, 1985 (cf. especially pages 17 and 238). Asillustrations of these electron-withdrawing groups, mention may be madeespecially of NO₂, quaternary ammonium, Rf and especially CF₃, CHO, CNand COY groups with Y possibly being a chlorine, bromine or fluorineatom or an alkyloxy group.

[0013] The halogen-halogen exchange reactions mentioned above in factconstitute the main synthetic route for gaining access to fluorinatedaromatic derivatives.

[0014] Thus, one of the techniques most widely used for manufacturing afluorinated derivative consists in reacting a halogenated, generally achlorinated, aromatic derivative, to exchange the halogen(s) with one ormore fluorine(s) of mineral origin. An alkali metal fluoride isgenerally used, usually one of high atomic weight, for instance sodiumfluoride and especially potassium, cesium and/or rubidium fluoride.

[0015] In general, the fluoride used is potassium fluoride, whichconstitutes a satisfactory economic compromise.

[0016] Under these conditions, many processes, for instance thosedescribed in the French certificate of addition No. 2 353 516 and in thearticle Chem. Ind. (1978)-56 have been proposed and used industrially toobtain aryl fluorides, on which aryls are grafted electron-withdrawinggroups, or alternatively aryls that are naturally electron-poor, forinstance pyridine nuclei.

[0017] However, except in the case where the substrate is particularlyadapted to this type of synthesis, this technique has drawbacks, themain of which are those that will be analyzed hereinbelow.

[0018] The reaction is slow and, on account of a long residence time,requires large investments. This technique, as has already beenmentioned, is generally used at high temperatures that may be up toabout 250° C., or even 300° C. in the case of electron-poor nuclei, iein the zone in which the stablest organic solvents begin to decompose.

[0019] The yields remain relatively mediocre unless particularlyexpensive reagents are used, for instance fluorides of an alkali metalwith an atomic mass higher than that of potassium.

[0020] Finally, given the price of these alkali metals, their industrialuse is justifiable only for products of high added value and when theimprovement in the yield and the kinetics justify it, which is rarelythe case.

[0021] To solve or overcome these difficulties, many improvements havebeen proposed. Thus, novel catalysts are proposed, and mention may bemade especially of tetradialkylaminophosphoniums and especially thosedescribed in the patent applications filed in the name of the Germancompany Hoechst and its subsidiary companies Clariant and Aventis (forexample U.S. Pat. No. 6,114,589; U.S. Pat. No. 6,103,659; etc.) and inthe patent applications filed in the name of the company Albemarle.

[0022] These novel catalysts do, admittedly, present a number ofadvantages over common catalysts, but afford no advantage in terms oftheir price and their complexity.

[0023] Consequently, one of the aims of the present invention is toprovide nucleophilic substitution catalysts that especially allow acatalysis of SN₂ and above all SN_(Ar) reactions.

[0024] Another aim of the present invention is to provide nucleophilicsubstitution catalysts that especially allow a catalysis of SN_(Ar)reactions, even when the nucleus that is the site of said SN_(Ar) isonly weakly electron-poor.

[0025] Another aim of the present invention is to provide nucleophilicsubstitution catalysts that are also phase-transfer agents.

[0026] Another aim of the present invention is to provide nucleophilicsubstitution catalysts that have a relatively high decompositiontemperature, for example at least equal to 200° C., advantageously 250°C. and even 300° C.

[0027] These aims, and others which will emerge hereinbelow, areachieved by means of use, as a catalyst for nucleophilic substitution,of a compound of general formula (I):

[0028] in which:

[0029] R₁, R₂, R₃, R₄, R₅ and R₆, which may be identical or different,are chosen from hydrocarbon-based radicals, one of the radicals R₁ to R₆possibly being a hydrogen when the other radicals R₁ to R₆ are such thatthe molecule contains more than one and preferably more than twosequence(s) Pn═Z═Pn (in this case, one, or more, Pn may be common toseveral sequences and Pn is advantageously P and Z is advantageously N);

[0030] the Pn, which are advantageously the same, are chosen from themetalloid elements of column V from a period higher than that ofnitrogen;

[0031] Z is a metalloid element from column V, which is advantageouslydifferent than Pn, preferably a nitrogen (N, P, As or Sb).

[0032] The fact that one of the radicals R₁ to R₆ is hydrogen is notpreferred.

[0033] The compounds of formula (I) may be neutral, and in this casethey are amphoteric, in other words they bear within the same moleculethe cationic function shown in formula (I) and the anionic function thatensures electrical neutrality; however, the compounds of formula (I)that are the easiest to use are cationic compounds and areadvantageously introduced in the form of a salt of formula (II):

[0034] in which:

[0035] X⁻ is a counterion chosen from anions and mixtures of anions,which anions and mixtures of anions are advantageously chosen frommonovalent anions;

[0036] said hydrocarbon-based radicals R₁, R₂, R₃, R₄, R₅ and R₆ aregenerally chosen from:

[0037] alkyls;

[0038] optionally substituted aryls;

[0039] amino and imino groups, advantageously in which the nitrogenlinked to a Pn does not bear hydrogen; among the amino groups,N,N-dialkylamino, N,N-diarylamino and N-aryl-N-alkylamino groups arepreferably chosen; among the imino groups that are particularly suitableare mono- and diarylketimino, phosphinimino, and especially trialkyl-,dialkylaryl-, diarylalkyl- and triarylphosphinimino, derivatives ofamidine type [of formula >N—C(—)═N— in which (—) represents an openbond] including cyclic forms and including guanidines [(>N—)₂C═N—)] maybe attached to the Pn via their amine function or via their iminefunction;

[0040] phosphino groups, such as dialkylphosphino, alkylarylphosphinoand especially diarylphosphino; however, especially when Pn isphosphorus, it is preferable for there to be not more than two andadvantageously not more than one such group per Pn atom;

[0041] hydrocarbyloxy groups;

[0042] a polymer arm.

[0043] As will be seen later, the compounds in which the radicals R₄, R₅or even R₆ are phosphinimino are easy to synthesize. Among thesephosphinimino groups, mention may be made of those in which thephosphorus bears aryl, alkyl or dialkylamino groups.

[0044] The aryl groups forming part of the above compound areadvantageously homocyclic, taken in the sense antonymous toheterocyclic.

[0045] The term “alkyl” is taken in its etymological sense as an alcoholresidue from which the OH function has been removed. Thus, itessentially comprises radicals in which the free bond is borne by acarbon atom sp³ hybridization, this carbon atom being linked only tocarbons or hydrogens. In the context of the present invention, among thealkyls that may also be mentioned are the compounds of formulaC_(n)H_(2n+1), alkyls which are substituted with atoms and/or functions(depending on the application, it is preferable, in order to avoid sidereactions, to select functions that are inert under the workingconditions of the invention) and especially those bearing etherfunction(s) and in particular the mono-, oligo- or polyethoxylatedchains derived from epoxides, especially of ethylene and/or of aperalkylated amine function, those which are substituted with halogens,and those bearing one or more aromatic nuclei.

[0046] Said alkyls may also bear quaternary ammonium or phosphoniumfunctions.

[0047] Except when they represent an arm, the radicals R₁, R₂, R₃, R₄,R₅ and R₆ advantageously contain not more than 20 carbon atoms, and,unless it is linked to a polymer, the molecule comprises in total notmore than 100 carbon atoms and preferably not more than 60 carbon atoms.

[0048] It is preferable for not more than 2 of the radicals R₁, R₂, R₃,R₄, R₅ and R₆ to represent a polymer arm; this arm is linked to thecorresponding Pn atom via a bond with a carbon atom of aliphatic oraromatic nature or via a bond with an imino or amino group.

[0049] However, it is more practical to use molecules that are notlinked to a polymer.

[0050] For reasons of ease of synthesis, it is preferable for R₁, R₂ andR₃ to be identical. This is likewise the case for R₄, R₅ and R₆.

[0051] The radicals R₁, R₂, R₃, R₄, R₅ and R₆ may be linked together andmay form rings.

[0052] In particular:

[0053] R₁, R₂ and R₃ may be linked together and may form rings, and

[0054] R₄, R₅ and R₆ may be linked together and may form rings.

[0055] When the Pn are the same, the synthesis of the catalysts in whichthe radicals R₁, R₂, R₃, R₄, R₅ and R₆ are the same is easier andtherefore less expensive. They are therefore preferred in this respect.However, the activity of the compounds not comprising this symmetryaround Z is very frequently excellent.

[0056] As has been mentioned above, when said hydrocarbon-based radicalsR₁, R₂, R₃, R₄, R₅ and R₆ are linked via a carbon to the atoms Pn, thiscarbon atom may be of sp³ aliphatic hybridization, or of sp²hybridization, ie especially of aromatic nature on account of theinstability of the vinyl groups. Links with atoms of aromatic nature arepreferred. Another kind of link is preferred, which is the link via thenitrogen atom of an amine function or of an imine function.

[0057] Thus, it is desirable for at least 3, advantageously at least 4,preferably at least 5 and more preferably all of the radicals R₁, R₂,R₃, R₄, R₅ and R₆ to be linked to the Pn via an aromatic carbon atomand/or a nitrogen atom of a peralkylated amine or imine function.

[0058] When the peralkylated imines are phosphonimines, this results inseveral sequences of the type Pn═N═Pn with one common atom Pn; in thiscase, to ensure solubility in solvents when the molecule is symmetricalof order 4 (four identical substituents) around a phosphorus, it ispreferable for there to be a number of carbon atoms greater by at leasta third and advantageously by at least a half of the sum of the nitrogenand phosphorus atoms.

[0059] The counterions are advantageously chosen from sparinglynucleophilic anions and mixtures of anions X⁻, ie, when they are single,they are such that XH has a pKa of not more than 3, advantageously 2,preferably 1 and more preferably zero, and when they consist of amixture of anions, at least one of the anions is sparingly nucleophilic.

[0060] It should be mentioned, however, that the counterionscorresponding to the superacids weaken the catalytic effect; thus,bromide is more effective than BF₄ ⁻. Thus, wherever it is possible andwhen the catalysis needs to be strong, it is preferable to avoidcounteranions that correspond to a high Hammett constant and thus toselect anions corresponding to acids with a Hammett constant of not morethan 12 and preferably 10.

[0061] According to one of the preferred embodiments of the invention,this use is implemented in a process that is useful for performing anucleophilic substitution of SN_(Ar) type on an aromatic substrate,characterized in that an aromatic substrate of general formula (III):

Ar-(Ξ)

[0062] in which Ar is an aromatic radical in which the nucleus bearing Ξis electron-poor either because it comprises at least one hetero atom inits ring, or because the sum of the σ_(p) of its substituents, besidesthe Ξ, is at least equal to 0.2, advantageously 0.4 and preferably 0.5;the substituents possibly being leaving groups capable of giving rise toa new substitution and thus of being noted Ξ, in a subsequent SN_(Ar);

[0063] in which Ξ is a leaving group, advantageously in the form of ananion Ξ⁻;

[0064] is subjected to the action of a nucleophilic agent capable ofexchanging with the or at least one of the substituents Ξ in thepresence of a catalyst of formula (I).

[0065] It is desirable for the molar ratio between the catalyst and thenucleophilic agent used in the reaction to be at least equal to 0.1%,advantageously 0.5%, preferably 1% and more preferably 0.5%.

[0066] It is also desirable for the molar ratio between the catalyst andthe substrate used in the reaction to be at least equal to 0.1%,advantageously 0.5%, preferably 1% and more preferably 0.5%.

[0067] Strictly speaking, there is no upper limit, but, unless thecompound of formula II is used as the reagent that is the vector of X⁻,which is then the nucleophile, it is more economical for the molar ratiobetween the catalyst and the nucleophilic agent used in the reaction tobe not more than ⅓, advantageously ⅕ and preferably 10%.

[0068] Advantageously, Ξ⁻ is less nucleophilic than the nucleophilicagent with which it exchanges; since the nucleophilicity scales aredifficult to use, a person skilled in the art may use the empirical rulethat ΞH is advantageously more acidic than the nucleophile in protonatedform. Ξ may be a nitro or quaternary ammonium group, but it ispreferable for it to be a pseudohalogen group or, preferably, a halogenatom chosen from chlorine, bromine and iodine.

[0069] The term “pseudohalogen” is intended to denote a group whose lossleads to an oxygenated anion, the anionic charge being borne by thechalcogen atom, and whose acidity, expressed by the Hamett constant, isat least equal to that of acetic acid, advantageously to the secondacidity of sulfuric acid and preferably to that of trifluoroacetic acid.

[0070] Illustrations of pseudohalogens of this type that may bementioned in particular include the anions corresponding to sulfinicacid and sulfonic acid, which are advantageously perhalogenated on thesulfur-bearing carbon, and also carboxylic acids that are perfluorinatedα to the carboxylic function.

[0071] Since the nucleophilic substitution reaction is relativelyfacilitated when Ξ represents an iodine atom, the process claimed ismore particularly advantageous when Ξ symbolizes a chlorine or bromineatom or a pseudohalogen.

[0072] As regards the substituent(s) of Ar, occasionally referred to as“groups R”, they are present on the aromatic nucleus, and are selectedsuch that they induce an overall depletion of electrons on the nucleusthat is sufficient to allow the activation of the substrate and thestabilization of the Meisenheimer complex (cf. indication given above).

[0073] The aromatic substrate thus substituted has an electron densityat most equal to that of phenyl, advantageously at most in the region ofthat of a chlorophenyl and preferably of a difluorophenyl.

[0074] This depletion may also be due to the presence in the aromaticring of a hetero atom such as, for example, in pyridine or quinoline. Itis important to point out that this type of depletion is observed onlywhen Ar symbolizes a compound with a 6-membered ring and the hetero atombelongs to column V (essentially nitrogen or phosphorus) as defined inthe Periodic Table of the Elements published in the supplement to theBulletin de la Société Chimique de France in January 1966.

[0075] Preferably, the group or at least one of the groups R is anon-leaving electron-withdrawing substituent and more preferably isother than a carbon-based substituent.

[0076] The substituent(s) R when they are withdrawing may be chosen fromhalogen atoms and the following groups:

[0077] NO₂

[0078] SO₂Alk and SO₃Alk

[0079] Rf and preferably CF₃

[0080] CN

[0081] CHO

[0082] COAlk

[0083] COΞ′, in which Ξ′ is chosen from the same values as Ξ, with thesame preferences

[0084] COOAlk

[0085] phosphone and phosphonate

[0086] with the symbol Alk representing a hydrogen or, advantageously, alinear or branched, preferably C₁ to C₄ alkyl group.

[0087] Examples of preferred groups R that may be mentioned moreparticularly include halogen atoms and the nitro group.

[0088] The electron-withdrawing substituent(s) R is(are) more preferablylocated in an ortho and/or para position relative to the leavinggroup(s) Ξ.

[0089] As regards the nucleophilic agent intended to replace the leavinggroup(s) X on the aromatic substrate, it may be generated in situ duringthe irradiation reaction.

[0090] As nucleophilic agents that may be used according to theinvention, mention may be made especially of:

[0091] phosphine, arsine and ammonia,

[0092] phosphines, arsines and amines, and anions thereof,

[0093] water and its anion,

[0094] alcohols and alkoxides,

[0095] hydrazines and semicarbazides,

[0096] salts of weak acids such as carboxylates, thiolates, thiols andcarbonates,

[0097] cyanide and its salts,

[0098] malonic derivatives, and

[0099] imines.

[0100] The nitrogenous nucleophilic derivatives are of most particularadvantage in the context of the claimed process.

[0101] Nucleophilic agents whose nucleophilic function is an anion givegood results.

[0102] Another aim of the present invention is to provide a process thatis especially useful for performing exchange reactions between fluorineand halogens with a higher atomic number present on the aromaticsubstrate, and especially exchange reactions between fluorine andchlorine.

[0103] Reverse exchange reactions, ie the replacement of one halogenwith a halogen of a higher row, are also possible. However, this type ofreaction is less advantageous and is also more difficult to perform.Nevertheless, it is within the capability of a person skilled in the artto exploit the teaching of the present process to perform other exchangereactions, and especially these reverse exchange reactions.

[0104] In the case of exchange reactions between fluorine and halogenswith a higher atomic number, the use of a fluoride as nucleophilic agentis preferred.

[0105] Advantageously, the fluoride is a fluoride of an alkali metalwith an atomic number at least equal to that of sodium, and ispreferably a potassium fluoride.

[0106] The alkali metal or alkaline-earth metal fluoride is at leastpartially present in the form of a solid phase.

[0107] In general, the reaction is performed at a temperature below thatselected for a reaction performed with a common catalyst (the ultimateexample of which is tetramethylammonium).

[0108] The reaction is generally performed in a solvent and, in thiscase, it is preferable to perform the reaction at a temperature at least10° C., advantageously 20° C. and preferably 40° C. below the limittemperature usually accepted for said solvent used.

[0109] A continuous recovery of the most volatile compounds may also beperformed gradually as they are formed. This recovery may be performed,for example, by distillation.

[0110] According to one of the possible embodiments, the heating isperformed partially or totally by microwaves of the present invention;in this case, it is preferable for the microwaves to be emitted overshort periods (from 10 seconds to 15 minutes) alternating with phases ofcooling. The respective durations of the microwave emission periods andof the cooling periods are chosen such that the temperature at the endof each microwave emission period remains below an initial settemperature, which is generally less than the resistance temperature ofthe ingredients of the reaction mixture.

[0111] It is also possible to perform such a heating according to aprocedure in which the reaction mixture is simultaneously subjected tomicrowaves and to cooling. According to this variant, the power releasedby the microwaves is then chosen such that, for an initial settemperature which is generally the working temperature, it is equivalentto the energy removed by the cooling system, plus or minus the heatevolved or absorbed by the reaction.

[0112] Such an actinic heating process moreover has the advantage ofbeing compatible with a continuous functioning mode. This mode of useadvantageously makes it possible to surmount the heat exchange problemsthat may arise during the operations of opening and closing of thereactor in which the microwaves are emitted.

[0113] According to this mode of functioning, the materials to beactivated are introduced continuously via an inlet orifice into thereactor, where they undergo an activation by microwaves and theactivated products are removed continuously from said reactor via anoutlet orifice.

[0114] In the case of actinic heating by microwave, it is recommended touse a power evolved by the microwaves of between 1 and 50 watts permilliequivalent of aromatic substrate. It is also desirable to acceptthe constraint according to which the power evolved by the microwaves isbetween 2 and 100 watts per gram of reaction mixture.

[0115] The catalyst according to the invention may be used concomitantlywith a catalyst acknowledged as being a phase-transfer catalyst,especially when this catalyst is a catalyst of cationic nature.

[0116] Such a concomitant use is all the more appropriate since themechanism of action appears to be different.

[0117] The best phase-transfer catalysts that may be used are generallyoniums, ie they are organic cations whose charge is borne by ametalloid. Among the oniums that may be mentioned are ammoniums,phosphoniums and sulfoniums. However, other phase-transfer catalysts mayalso be used provided that the phase-transfer catalysts are positivelycharged. They may also be cryptand cations, for examplealkali-metal-cryptand crown ethers.

[0118] These phase-transfer catalysts may be used in the presence orabsence, preferably in the presence, of an alkali metal cation that isparticularly heavy and thus from a high atomic row, such as cesium andrubidium.

[0119] When the present invention is used to carry out achlorine/fluorine exchange reaction, a dipolar aprotic solvent, a solidphase consisting at least partially of alkali metal fluorides and areaction-promoting cation are generally used, said cation being a heavyalkali metal or an organic phase-transfer agent, this agent being ofcationic nature.

[0120] The content of alkali metal cation, when it is used as promoter,is advantageously between 1 mol % and 5 mol % and preferably between 2mol % and 3 mol % of the nucleophilic agent used. These ranges areclosed ranges, ie they include their limits.

[0121] The reagent may comprise, as promoter, phase-transfer agents thatare oniums (organic cations whose name ends with onium). The oniums ingeneral represent 1 mol % to 10 mol % and preferably from 2 mol % to 5mol % of the aromatic substrate, and the counterion may be of any naturebut is usually halogenated.

[0122] Among the oniums, the preferred reagents are tetraalkylammoniumsof 4 to 28 carbon atoms and preferably from 4 to 16 carbon atoms. Thetetraalkylammonium is generally tetramethylammonium.

[0123] Phosphoniums and especially phenylphosphoniums should also bementioned, which have the advantage of being stable and relativelysparingly hygroscopic; however, these reagents are relatively expensive.

[0124] The aprotic solvent of halex type advantageously has asignificant dipolar moment. Thus, its relative dielectric constantepsilon is advantageously at least equal to about 10; preferably, theepsilon is less than or equal to 100 and greater than or equal to 25.

[0125] It has been possible to show that the best results were obtainedwhen dipolar aprotic solvents with a donor index of between 10 and 50were used, said donor index being the ΔH (enthalpy variation) expressedin kilocalories of the combination of said dipolar aprotic solvent withantimony pentachloride.

[0126] The oniums are chosen from the group of cations formed by columnsVB and VIB as defined in the Periodic Table of the Elements published inthe supplement to the Bulletin de la Société Chimique de France inJanuary 1966, with four or three hydrocarbon-based chains, respectively.

[0127] In general, it is known that a fine particle size has aninfluence on the kinetics. Thus, it is desirable for said solid insuspension to have a particle size such that its d₉₀ (defined as themesh that allows 90% by mass of the solid to pass through) is not morethan 100 μm, advantageously not more than 50 μm and preferably not morethan 200 μm. The lower limit is advantageously characterized in that thed₁₀ of said solid in suspension is not less than 0.1 μm and preferablynot less than 1 μm.

[0128] In general, the ratio between said nucleophilic agent, preferablythe alkali metal fluoride, and said substrate is between 1 and 1.5 andpreferably in the region of 5/4 relative to the exchange stoichiometry.

[0129] The mass content of solids present in the reaction medium isadvantageously not less than ⅕, advantageously ¼ and preferably ⅓.

[0130] The stirring is advantageously performed such that at least 80%and preferably at least 90% of the solids are maintained in suspensionby the stirring.

[0131] According to the present invention, the reaction isadvantageously performed at a temperature ranging from about 150 toabout 250° C. In the present description, the term “about” is used toillustrate the fact that the values that follow it correspond tomathematic round-ups and especially that, in the absence of a decimalpoint, when the figure(s) the furthest to the right in a number arezeros, these zeros are positional zeros rather than significant figures,except, of course, if otherwise specified.

[0132] However, it should be pointed out that when the temperatureincreases, the kinetics increase but the selectivity decreases.

[0133] Another aim of the present invention is to provide a compositioncapable of serving as a reagent for nucleophilic substitution,especially aromatic nucleophilic substitution.

[0134] This aim is achieved by means of a composition comprising:

[0135] a polar aprotic solvent;

[0136] a nucleophile;

[0137] a compound of formula (I)

[0138] It should be noted that the compounds of formulae (I) and (II)are particularly suitable for the usual recycling techniques.

[0139] Another aim of the invention is to provide, besides that ofhaving provided a novel family of novel compounds that is useful asnucleophilic substitution catalysts having a pronounced catalyticnature.

[0140] Another aim of the present invention is to provide a process forsynthesizing compounds that are used or that may be used as catalystsfor second order nucleophilic substitution and especially for SN_(Ar)nucleophilic substitution.

[0141] These aims have been achieved with compounds of formula (I) inwhich the number of alkyl substituents is not more than 2 and in whichthe total number of carbons is not less than 14 and preferably 16 perpositive charge borne by the molecule. It should also be pointed outthat it is particularly advantageous to have molecules that are notcompletely symmetrical around one of the atoms Z, but also around one ofthe atoms Pn.

[0142] Thus, it may be indicated that the sum of the carbons in theradicals R₁, R₂, R₃, R₄, R₅ and R₆ is greater than 12, preferably notless than 14 and advantageously not less than 16.

[0143] The condition regarding the alkyls may also be expressed byindicating that not more than 2 and preferably not more than one of theradicals R₁, R₂ and R₃, on the one hand, and/or R₄, R₅ and R₆, on theother hand, represent an alkyl group.

[0144] Finally, when symmetry is not desired, the absence of symmetryrelative to Z may be expressed by indicating that the combinationconsisting of R₁, R₂ and R₃ must be different, for at least one of thesecomponents, than the combination R₄, R₅ and R₆. As regards thenon-symmetry around one of the Pn when it is desired, this absence ofsymmetry may be expressed in the following manner: at least one of theradicals R₄, R₅ and R₆ must be different than the radical consisting of(R₁) (R₂) (R₃)P_(n)═N—.

[0145] The limitation regarding the number of alkyl derivatives islinked to the fact that, according to the present invention, it has beenshown that it was desirable for the substituents R₁, to R₆ especially tohave a donor nature via a mesomeric effect, so as to delocalize thepositive charge better. However, alkyl chains with a carbon number ofgreater than 5 may be advantageous for the compatibility of the catalystwith solvents of sparingly polar nature, ie solvents that are notmiscible in all proportions with water.

[0146] According to the present invention, the targeted compounds may besynthesized by the action of an iminoid of formula (R₁) (R₂)(R₃)P_(n)═ZH or derivatives thereof on suitable substrates, namelytrivalent Pn compounds.

[0147] According to one of the modes of preparation, the iminoid inhydrogenated form or in the form of a salt, advantageously an alkalimetal salt, is reacted with a trivalent Pn derivative [halogen >Pn-X inwhich X represents a leaving group] bearing a leaving group,advantageously halogen (preferably bromine or chlorine) the iminoidanion replaces the leaving group giving a sequence Pn═Z-Pn<. The finalproduct may be obtained by quaternizing the Pn that has remainedtrivalent using a compound chosen from R₄-X′, R₅-X′ and R₆-X′, in whichX′ is a leaving group, advantageously a halogen, preferably from a rowat least equal to that of chlorine; and especially bromine and iodine.

[0148] The reaction may be written in the manner below:

[0149] The quaternization reaction takes place at the end, and reactionsto introduce the radicals R₄ and R₅ may take place in between.

[0150] For example, several iminoid groups may be grafted:

[0151] Usually, in this route, the iminoid is condensed with a phosphinealready bearing two final substituents, in this case R₄ and R₅.

[0152] In this case also, one of the Pn, preferably both of them,is(are) advantageously P. Z is advantageously nitrogen.

[0153] According to another mode of action, the anion of the iminoid isconverted into a cation by oxidation, advantageously using a positivehalogen (commonly written in the case of bromine as Br⁺) or a molecularhalogen, usually bromine, and is placed in contact with a trisubstitutedPn (R₄) (R₅) (R₆)Pn; thus directly giving a compound according to thepresent invention. This technique is developed further:

[0154] In this case also, one of the Pn, and preferably both of them,is(are) advantageously P. Z is advantageously nitrogen.

[0155] The reactivity and the polyvalency of (R₁) (R₂) (R₃)P_(n)═ZH, andof the alkali metal salts thereof (where appropriate in the presence ofmolecular halogen, usually bromine) and especially those of (R₁) (R₂)(R₃) P═NLi makes it possible to perform many catalyst syntheses, whetheror not the molecules are already known. Its use constitutes anadvantageous route of access for the compounds used as catalyst in thepresent invention. The reactions in the examples below are typicalexamples thereof.

[0156] According to another embodiment of the present invention, thesynthesis may be performed by reacting a trisubstituted phosphiniminecompound with a halophosphonium halide, which phosphonium bears threehydrocarbon-based substituents. The halophosphonium halide:

[0157] may be produced in situ by the action of a halide on a phosphine.The reaction may be written as below, in which the condensation exampletaken is the condensation of a phosphinimine with a triphenylphosphinein the presence of bromine.

[0158] In this case, the synthesis of the phosphiniminophosphoniumbromide may be performed by reacting phosphinimines withdibromophosphoranes corresponding to the desired salt. Thephosphinimines are obtained by deprotonating the correspondingaminophosphonium salt in the presence of a strong base such as sodiumamide.

[0159] The reaction may be written as below:

[0160] In this equation, the radicals R′ may correspond, for example, toR₁, R₂ and R₃, and the radicals R may correspond to R₄, R₅ and R₆, orvice versa.

[0161] As regards the procedure, two options are possible, one reactingthe phosphinimine with the preformed dibromophosphorane, anotherreacting this same phosphinimine with bromine and then with theappropriate phosphine.

[0162] Needless to say, the technique is performed under an atmosphereof dry inert gas. The starting phosphonimines are generally obtained bythe action of one equivalent of N-butyllithium as base on anaminophosphonium halide, generally the bromide. Certain phosphiniminesare commercially available. Dibromophosphorane is prepared beforehand bysimple addition of a stoichiometric amount of dibromine to theappropriate phosphine. As indicated in the typical equation below:

[0163] In this equation, the radicals R′ may correspond, for example, toR₁, R₂ and R₃, and the radicals R may correspond to R₄, R₅ and R₆, orvice versa.

[0164] According to one variant already mentioned above of the presentinvention, the synthesis of these symmetrical or dyssymmetricalcompounds is performed using an intermediate known as a phosphoniumazayldiide. This reaction may be represented schematically as below, itbeing understood, of course, that, in this example, the phenyls may bereplaced with R₁, R₂, R₃ and Ar₃ may be replaced with R₄, R₅ and R₆.

[0165] The method described [lacuna] to gain access to tribromoderivatives. By using only one equivalent of bromine (instead of 2), themonobromo salts are synthesized directly.

[0166] In this equation, the radicals R′ may correspond, for example, toR₁, R₂ and R₃, and the radicals R may correspond to R₄, R₅ and R₆, orvice versa.

[0167] This simple method makes it possible to obtain, in the samereaction medium (R₃PNLi is prepared in situ by the action of 2equivalents of BuLi on the corresponding aminophosphonium salt) thedesired phosphiniminophosphonium salts under very mild conditions andvery quickly.

[0168] Needless to say, salts other than the lithium salts may be used,but the lithium salt is the easiest to manufacture using butyllithium.The reactions are performed in common solvents, generally in optionallycyclic ethers, for instance THF, or chlorinated derivatives, forinstance dichloromethane, the temperature usually used being between−30° C. and room temperature, more generally between −20° C. and roomtemperature.

[0169] The examples that follow are given as non-limiting illustrationsof the invention:

EXAMPLE 1

[0170] Preparation of 4-Fluoronitrobenzene: Comparison With“Already-Known Catalysts” Procedure

[0171] The following are introduced into a 60 ml tube:

[0172] para-chloronitrobenzene

[0173] DMSO

[0174] the catalyst

[0175] KF.

[0176] The tubes are closed with a septum and a screw stopper, and thenheated with stirring for 4 hours at 150° C. After cooling to roomtemperature, about 10 g of water are added, followed by 5 g ofdichloromethane, and, after settling of the phases and separation of theorganic and aqueous phases, the aqueous phase is back-extracted twicewith 5 g of dichloromethane. The various organic phases are combined andanalyzed by GC. Charge table KF Catalyst PCNB KF equiva- DMSO Catalystequiva- mass mass lent/ mass Catalyst mass lent/ Test (g) (g) pCNB (g)nature (g) pCNB A 5.0087 2.03 1.10 5 0 0 B 5.0062 2.03 1.10 5 TMAC0.1086 0.031 C 5.0048 2.03 1.10 5 Bu₄PBr 0.3237 0.030 D 5.0049 2.04 1.115 Tetrakis 0.381 0.030 E 5.0089 2.03 1.10 5 Ph₄PBr 0.4002 0.030 F 5.0042.03 1.10 5 PPNCl 0.548 0.030 TMAC = tetramethylammonium chloride Bu₄PBr= tetrabutylphosphonium bromide tetrakis =tetrakis(diethylamino)phosphonium bromide Ph₄PBr =tetraphenylphosphonium bromide PPNCl =bis(triphenylphosphoranylidene)ammonium chloride of formula:

[0177] Results Degree of Catalyst conversion of Test nature the pCNBYield of PFNB A 7 4 B TMAC 46 46 C Bu₄PBr 15 15 D Tetrakis 17 17 EPh₄PBr 11 6 F (according to PPNCl 62 62 the invention)

[0178] It is noted that the catalyst according to the invention is byfar the best catalyst, as regards both the reaction selectivity and thedegree of conversion.

EXAMPLE 2

[0179] Preparation of 2,4-Difluoronitrobenzene: Comparison With“Already-Known Catalysts”

[0180] Procedure

[0181] The following are introduced into a 60 ml tube:

[0182] 2,4-dichloronitrobenzene

[0183] sulfolane

[0184] the catalyst

[0185] KF.

[0186] The tubes are closed with a septum and screw stopper, and arethen heated with stirring for 4 hours at 170° C. After cooling to roomtemperature, about 10 g of water are added, followed by 5 g ofdichloromethane, and, after settling of the phases and separation of theorganic and aqueous phases, the aqueous phase is back-extracted twicewith 5 g of dichloromethane. The various organic phases are combined andanalyzed by GC. Charge table KF Sulfolane Catalyst Catalysts DCNB KFequivalent/ mass Catalyst mass equivalent/ Test mass (g) mass (g) DCNB(g) nature (g) DCNB A 5.0062 3.33 2.2 6.3 0 0 B 5.0026 3.34 2.2 6.3 TMAC0.0868 0.031 C 5.0084 3.33 2.2 6.3 Bu₄PBr 0.266 0.030 D 5.0149 3.34 2.26.3 Tetrakis 0.312 0.030 E 5.0066 3.34 2.2 6.3 Ph₄PBr 0.358 0.030 F5.0092 3.34 2.2 6.3 PPNCl 0.449 0.030

[0187] Results Degree of Catalyst conversion of Yield of Yield of Testnature the DCNB CFNB DFNB A 25 20 2 B TMAC 97 29 68 C Bu₄PBr 95 27 67 DTetrakis 96 24 69 E Ph₄PBr 92 31 60 F PPNCl 98 16 77.5

[0188] The catalyst according to the invention [lacuna] which gives boththe best degree of conversion, but also the one which gives the bestyield of difluoro product.

EXAMPLE 3

[0189] Preparation of 1-fluoro-3,5-dichlorobenzene and1,3-difluoro-5-chlorobenzene: Examples for Comparison With“Already-Known Catalysts”

[0190] Procedure

[0191] The following are introduced into a 60 ml tube:

[0192] 1,3,5-trichlorobenzene

[0193] sulfolane

[0194] the catalyst

[0195] KF.

[0196] The tubes are closed with a septum and screw stopper, and arethen heated with stirring at 210° C. for the time indicated in thetable. After cooling to room temperature, about 10 g of water are added,followed by 5 g of dichloromethane, and, after settling of the phasesand separation of the organic and aqueous phases, the aqueous phase isback-extracted twice with 5 g of dichloromethane. The various organicphases are combined and analyzed by GC. Charge table TCB KF KF SulfolaneCatalyst Catalysts mass mass equivalent/ mass Catalyst mass equivalent/Test T (h) (g) (g) TCB (g) nature (g) TCB A 3 1.508 0.96 2 2 Bu₄PBr0.055 0.02 B 3 1.506 0.97 2 2 Bu₄PBr 0.143 0.05 C 2 1.503 0.97 2 2Tetrakis 0.099 0.03 D 2 1.505 0.97 2 2 PPNCl 0.143 0.03

[0197] Results Degree of conversion Catalyst of the TCB Yield of Yieldof Test nature (%) FDCB CDFB A Bu₄PBr 3 2.5 0 B Bu₄PBr 3 2.7 0 CTetrakis 3 2.9 0 D PPNCl 23 21 0.7

[0198] The catalyst according to the invention is on the one hand theone that gave the highest degree of conversion, but on the other handthe only one that gave a small amount of difluorination.

EXAMPLE 4

[0199] Preparation of 4-Fluoronitrobenzene

[0200] Procedure

[0201] The following are introduced in order into a 30 ml Schott tube:

[0202] 4-chloronitrobenzene

[0203] the catalyst

[0204] KF

[0205] DMSO.

[0206] The tubes are closed with a septum and screw stopper, and arethen heated with stirring for 3 hours at 150° C. After cooling to roomtemperature, about 10 g of water are added, followed by 5 g ofdichloromethane, then 5 g of dichloromethane again, and, after settlingof the phases and separation of the organic and aqueous phases, theaqueous phase is back-extracted twice with 5 g of dichloromethane. Thevarious organic phases are combined and analyzed by HPLC. Charge tableeq eq eq Mass Kf DMSO mass cat. PNCB to to catalyst in g to Test g PNCBPNCB nature catalyst PNCB 1 2.0092 1.11 3.00 Nothing 0 0 2 2.0493 1.103.00 [(CH₃)₂N]₃PNP 0.2261 0.041 [N(CH₃)₂]₃, BF⁴⁻ 3 2.1034 1.10 3.03[(CH₃)₂N]₃PNP 0.2495 0.041 Bu₃, Br⁻ 4 2.0962 1.10 3.00 Ph₃PNPBu₃, Br⁻0.2982 0.040 5 2.0111 1.13 3.01 [(CH₃)₂N]₃PNP 0.2186 0.041 [N(CH₃)₂]₃,Br⁻ 6 1.5620 1.09 3.23 Ph₃PNP- 0.1871 0.043 [N(CH₃)₂]₃, Br⁻ 7 1.51361.11 3.22 Ph₃PNP((o)- 0.2731 0.040 MeOPh)₃, Br− 8 1.5069 1.13 3.24Bu3PNPBu₃, Br− 0.1992 0.042 Ph₃PNP(Co)-MeOPh)₃, Br− =

[0207] Results Test Catalysts Yield of PNFB 1 Nothing  5.87% 2[(CH₃)₂N]₃PNP[N(CH₃)₂]₃, BF₄₋ 10.60% 3 [(CH₃)₂N]₃PNPBu₃, Br— 15.77% 4Ph₃PNPBu₃, Br— 28.00% 5 [(CH₃)₂N]₃PNP[N(CH₃)₂]₃, Br— 20.04% 6Ph₃PNP[N(CH₃)₂]₃, Br— 45.50% 7 Ph₃PNP((o)—MeOPh)₃, Br- 37.82% 8Bu₃PNPBu₃, Br— 41.83%

EXAMPLE 5

[0208] Preparation of 1,3,5-Trifluorobenzene

[0209] Procedure

[0210] The following are introduced in order into a 30 ml Schott tube:

[0211] 1,3,5-trichlorobenzene

[0212] the catalyst

[0213] KF

[0214] sulfolane.

[0215] The tubes are closed with a septum and screw stopper, and arethen heated with stirring for 3 hours at 210° C. After cooling to roomtemperature, about 10 g of water are added, followed by 5 g ofdichloromethane, then 5 g of dichloromethane again, and, after settlingof the phases and separation of the organic and aqueous phases, theaqueous phase is back-extracted twice with 5 g of dichloromethane. Thevarious organic phases are combined and analyzed by GC. Charge table eqeq Mass eq Kf sulfolane in g of cat. Mass to to Catalyst cata- to TestTCB g TCB TCB nature lysts TCB 1 1.541 2.07 2.25 Nothing 0 0 2 1.50302.08 2.02 [(CH₃)₂N]₃PNP 0.1579 0.041 Bu₃, Br⁻ 3 1.5076 2.01 2.03Ph₃PNPBu₃, Br— 0.1860 0.040 4 1.5095 1.99 2.02 [(CH₃)₂N]₃PNP 0.14080.040 [N(CH₃)₂]₃, Br— 5 1.4929 1.99 2.09 Ph₃PNP 0.1767 0.049 [N(CH₃)₂]₃,Br— 6 1.0082 2.08 2.29 Bu₃PNPBu₃, Br— 0.1616 0.058

[0216] Results Test Catalysts RY DCFB RY DFCB 1 Nothing  <0.5% <0.5% 2[(CH₃)₂N]₃PNPBu₃, Br 25.39% 1.04% 3 Ph₃PNPBu₃, Br— 15.70% 0.24% 4[(CH₃)₂N]₃PNP[N(CH₃)₂]₃, Br— 38.95% 2.73% 5 Ph₃PNP[N(CH₃)₂]₃, Br— 25.24%1.48% 6 Bu₃PNPBu₃, Br— 11.55% 1.28%

[0217] Synthesis of Catalysts

[0218] The reactivity and polyvalency of (R₁) (R₂) (R₃) Pn═ZH, and ofthe alkali metal salts thereof (where appropriate in the presence ofmolecular halogen, usually bromine) and especially those of (R₁) (R₂)(R₃) P═NLi, makes it possible to perform numerous syntheses ofcatalysts, whether or not the molecules are already known. Its useconstitutes an advantageous route of access for the compounds used ascatalyst in the present invention. The reactions below are examplesthereof.

EXAMPLE 6

[0219] Synthesis of Catalysts

[0220] The reaction of Ph₃P═NLi with PCl₃ leads quantitatively to thesynthesis of the protonated triphosphinimine 3. The synthesis of thiscompound is performed by passing via the corresponding triphosphinimine(Ph₃P═N)₃P; this compound has a lone pair on the phosphorus atom, theelectron density of which is considerably increased by the triple donoreffect of the three Ph₃P═N— groups. This triphosphinimine then becomesbasic enough to become protonated within a few minutes at 20° C.,probably by attacking the protons of THF, and precipitating in thissolvent in the form of the phosphonium salt [(Ph₃P═N)P—H]⁺Cl⁻.

[0221] This availability of the lone pair makes this compound anadvantageous intermediate for subsequent quaternization and to form acompound according to the invention.

[0222] Procedure

[0223] Trichlorophosphine (1.4 mmol, 1 equivalent) is added by syringein a single portion to a solution of Ph₃P═NLi (4.2 mmol, 3 equivalents)in 50 ml of THF at 20° C. The mixture is stirred at this temperature for30 minutes; a white precipitate ofN,N′,N″-(phosphinio)tris-triphenylphosphinimine then forms in themedium. This precipitate is filtered off, rinsed with THF and obtainedin pure form in a yield of 95%.

[0224] (Ph₃P═N)₃P is observed by ³¹P NMR after the action ofn-butyllithium on a solution of the isolated salt 3 in dimethylsulfoxide at 20° C. The triphosphinimine, which is very sensitive tomoisture and to oxygen, could not be isolated. After deprotonationfollowed by addition of elemental sulfur, a mixture of the startingphosphonium salt (12%) and of oxidized triphosphinimine (Ph₃P═N)₃P═O(52%) and sulfurized triphosphinimine (Ph₃P═N)₃P═S (24%) is recovered.

[0225] The pKa of the [(Ph₃P═N)₃P—H]⁺/(Ph₃P═N)₃P couple is between thatof Ph₃═P═NH/Ph₃P═NLi and that of the n-butane/n-butyllithium couple, iebetween 28 and 43.

EXAMPLE 7

[0226] Addition of one equivalent of chlorodiphenylphosphine toN-diphenylphosphinotriphenylphosphinimine 1, to give a phosphiniminecontaining a P═N—P—P sequence 2.

[0227] Ph₂PCl (4 nmol) is added dropwise at 20° C. to a solution ofN-diphenylphosphinotriphenylphosphinimine (4 mmol) in THF. The solutionis stirred for 12 hours at this temperature. Compound 2 precipitatesover time. The solution is then filtered, the white solid collected isthen recrystallized from acetonitrile and is obtained in a yield of 73%.Its structure is confirmed by melting point, mass spectrometry, ³¹P NMRand IR.

[0228] This compound has been described once in 1969 by Madersteig(Mardersteig, H. G.; Meinel, L.; Nöth, H. Z. Anorg. Allg. Chem. 1969,368, 254-261 or Z. Anorg. Allg. Chem. 1970, 375, 272-280) starting withPh₃P═NSiMe₃ and two equivalents of Ph₂PCl.

EXAMPLE 8

[0229] Synthesis of [Ph₃P═N═PBu₃]⁺Br⁻

[0230] 28 mmol of n-BuLi (as a commercial hexane solution: Aldrich) areadded dropwise over about 15 minutes to a solution of 14 mmol ofaminotriphenylphosphonium bromide in 125 ml of anhydrous THF, cooled to−15° C. The mixture is stirred constantly at this temperature for onehour (the diylide thus generated may be analyzed by phosphorus NMR,taking the precaution of performing the withdrawal under nitrogen).Under these conditions, 14 mmol (1 equivalent) of bromine predried bymeans of an acidic wash (36% H₂SO₄) are added. The reaction mixture isthen stirred for 2 hours at a temperature of 0 to 5° C. 14 mmol oftributylphosphine are finally added to this solution. The mixtureobtained is stirred constantly for about 12 hours (overnight).

[0231] The solution obtained is filtered and the filtrate isconcentrated to dryness under reduced pressure. The ³¹P NMR analysisshows the majority presence of the expected product. The residue thusrecovered is taken up in dichloromethane and washed with distilled watersolution. The organic phase is dried over MgSO₄ and then concentrated todryness. The product is redissolved in a minimum amount ofdichloromethane and purified by adding a large volume of ether. Therecovered product is subjected to ion exchange using a sodium iodide NaIsolution in order to facilitate its purification ^(a)). After thistreatment, the residue is taken up in 20 ml of ether and left under coldconditions (4° C.) for 3 hours. The iodinated product precipitates andis recovered in pure form by simple filtration.

[0232] The product in its brominated form will be obtained by simple ionexchange first using an AgNO₃ solution and then with an NaBr solution^(b)). The oil obtained is left in the open air for several days inorder to obtain a crystalline solid.

[0233] The impure bromo residue recovered is taken up in dichloromethaneand washed successively with 3 aqueous NaI solutions of concentration:(2.5 eq; 1.5 eq; 0.5 eq). The organic phase is then dried over MgSO₄ andconcentrated to dryness in view of the various treatments.

[0234] The pure iodide obtained is redissolved in dichloromethane andwashed with aqueous silver nitrate solution (2 eq). The organic phase isthen washed with distilled water solution to remove the silver iodideresidues in suspension. The organic phase then undergoes 3 washes withan aqueous NaBr solution (2.5 eq; 1.5 eq; 0.5 eq). The organic solutionis finally dried over MgSO₄ and then concentrated to dryness underreduced pressure, thus allowing the pure bromo compound to be isolated.

[0235]³¹P NMR (ppm) (CDCl₃): 41.14 (s, ^((a))P; 17.28 (s, ^((b))P)

[0236]¹H NMR (ppm) (CDCl₃): 7.7-7.58 (m, 15H, aromatic); 1.98 (m, 6H,¹CH₂); 1.31 (m, 12H, ²CH₂—³CH₂—); 0.79 (t, 9H, CH₃)

[0237]¹³C NMR (ppm) (CDCl₃): 133.18 (d, J⁴ _(PC)=2.83 Hz, C₆H₅ p-C);131.31 (d, J³ _(PC)=11.16 Hz, C₆H₅ m-C); 128.14 (d, J² _(PC)=13.01 Hz,C₆H₅ o-C); 128.14 (d, J² _(PC)=13.01 Hz, C₆H₅ o-C); 127.69 (dd, J¹_(PC)=107.3 Hz, J³ _(PaC)=1.54 Hz, C₆H₅ ipso-C); 26.30 (d, J¹_(PC)=63.47 Hz, CH₂); 23.09 (d, J² _(PC)=15.88 Hz, CH₂); 23.11 (d, J³_(PC)=4.57 Hz, CH₂); 12.99 (s, CH₃)

[0238] Mass: FAB⁺ M-Br⁻; 478 [NBA matrix]

[0239] Microanalysis EXP.: C: 65.05%; H: 7.70%; P: 10.50% THEO.: C:64.45%; H: 7.51%; P: 11.10%; BR: 14.31%

EXAMPLE 9

[0240] Synthesis of [Ph₃P═N═P(o-C₆H₄OMe)₃]⁺Br⁻

[0241] a) Synthesis of [Ph₃P═N═P(o-C₆H₄OMe)₃]⁺Br₃ ⁻

[0242] 28 mmol of n-BuLi (as a commercial hexane solution: Aldrich) areadded dropwise over about 15 minutes to a solution of 14 mmol ofaminotriphenylphosphonium bromide in 125 ml of anhydrous THF, cooled to−15° C. The mixture is left under constant stirring at this temperaturefor one hour (the diylide thus generated may be analyzed by phosphorusNMR, taking the precaution to perform the withdrawal under nitrogen).Under these conditions, 35 mmol (2.5 equiv.) of a bromine solutionpredried by means of an acidic wash (36% H₂SO₄) are added. The reactionmixture is then stirred for 2 hours at a temperature of 0 to 5° C. 14mmol of tri-o-anisylphosphine are finally added to this solution. Themixture obtained is left under constant stirring for about 12 hours(overnight).

[0243] The solution obtained is filtered and the precipitate is purifiedby simple washing, first with a solution of 30 ml of ethanol and thenwith a solution of 50 ml of ether. The tribromo salt of the expectedproduct was obtained.

[0244]³¹P NMR (ppm) (CH₂Cl₂): 19.62 (d, ^((a))P, J² _(PP)=16.04 Hz);15.06 (s, ^((b))P), J² _(P-P)=16.04 Hz)

[0245]¹H NMR (ppm) (CDCl₃): 7.66-6.74 (m, 27H, aromatic); 3.16 (m, 9H,OCH₃)

[0246]¹³C NMR (ppm) (CDCl₃): 160.90 (d, J² _(PC)=2.98 Hz, C₆H₄ o-C-OMe);135.39 (d, Ar); 134.12 (d, Ani); 133.19 (d, Ani); 132.03 (d, Ar); 128.93(d); 128.03 (dd, J¹ _(PC)=111.27 Hz, J³ _(PC)=2.05 Hz, ipso-C-Ar);121.13 (d, J³ _(PC)=13.77 Hz, Ani); 115.12 (dd, J¹ _(PC)=116.50 Hz, J³_(PC)=2.05 Hz, ipso-C-Anisyl); 111.97 (d, J³ _(PC)=7.07 Hz, Ani); 55.25(s, OMe).

[0247] Mass: FAB⁺ M-Br⁻; 628 [NBA matrix]

[0248] Microanalysis EXP.: C: 53.19%; H: 4.13%; N: 1.72% THEO.: C:53.88%; H: 4.14%; N: 1.61%

[0249] b) Reduction of the Br₃ ⁻ to Br⁻

[0250] The tribromo salts obtained are taken up in a dichloromethanesolution and washed with aqueous sodium sulfite solution (2 eq).Decolorization of the organic phase is then rapidly observed, which isthe characteristic sign of reduction of the trihalides. The organicphase is dried over MgSO₄ and then concentrated to dryness under reducedpressure. The phosphorus, proton and carbon spectra are good, but themicroanalysis does not correspond either to the monobromo product or tothe tribromo product.

[0251] c) Synthesis of [Ph₃P═N═P(o-C₆H₄OMe)₃]⁺Br⁻

[0252] 28 mmol of n-BuLi (as a commercial hexane solution: Aldrich) areadded dropwise over about 15 minutes to a solution of 14 mmol ofaminotriphenylphosphonium bromide in 125 ml of anhydrous THF, cooled to−15° C. The mixture is left under constant stirring at this temperaturefor one hour (the diylide thus generated may be analyzed by phosphorusNMR, taking care to perform the withdrawal under nitrogen). Under theseconditions, 14 mmol (1 equivalent) of bromine predried by means of anacidic wash (36% H₂SO₄) are added. The reaction mixture is then stirredfor 2 hours at a temperature of 0 to 5° C. 14 mmol oftri-o-anisylphosphine are finally added to this solution. The mixtureobtained is left under constant stirring for about 12 hours (overnight).The solution obtained is filtered and the filtrate is concentrated todryness under reduced pressure. The ³¹P NMR analysis shows the majoritypresence of the expected product. The residue thus recovered is taken upin dichloromethane and washed with distilled water solution. The organicphase is dried over MgSO₄ and then concentrated to dryness. The productis redissolved in a minimum amount of dichloromethane and purified byadding a large volume of ether, from which it precipitates.

[0253]³¹P NMR (ppm) (CH₂Cl₂): 20.17 (d, ^((a))P, J² _(PP)=16.15 Hz);15.54 (s, ^((b))P), J² _(P-P)=16.15 Hz)

[0254]¹H NMR (ppm) (CDCl₃): 7.67-6.75 (m, 27H, aromatic); 3.19 (m, 9H,OCH₃) (ppm) (CDCl₃): 54.9 ppm (s, OCH₃ Ani); 111.6 ppm (d, ³J_(P-C)=6.7Hz, CH Ani ); 114.8 ppm (d, ¹J_(P-C)=112.1 Hz, C_(IV) Ani); 120.8 ppm(d, ³J_(PC)=13.8 Hz, CH Ani); 127.1 ppm (d, ¹J_(PC)=115.9 Hz, C_(IV)Ph); 128.9 ppm (d, ³J_(PC)=13.4

[0255]¹³C NMR Hz, CH Ph); 131.8 ppm (d, ²J_(PC)=11.5 Hz, CH Ph); 133.2ppm (d, ⁴J_(PC)=2.06 Hz, CH Ph); 133.9 ppm (d, ²J_(PC)=10.05 Hz, CHAni); 135.4 ppm (apparent s, ⁴J_(PC)≈0 Hz; CH Ani); 161.2 ppm (s, C-OMeAni)

[0256] Mass: FAB⁺ M-Br⁻; 628 [NBA matrix]

[0257] Microanalysis EXP.: AWAITING THEO.: C: 66.11%; H: 5.12%; BR:11.28%

EXAMPLE 10

[0258] Synthesis of [(Me₂N)₃-P═N═P-(NMe₂)₃]⁺Br⁻

[0259] Comment: In this case, we used iminotris(dimethylamino)phosphorane [(CH₃)₂N]₃P═NH as starting substrate. Consequently, only oneequivalent of n-BuLi is added to generate the corresponding azayldiide.

[0260] 14 mmol of n-BuLi (as a commercial hexane solution: Aldrich) areadded dropwise over about 15 minutes to a solution of 14 mmol ofiminotris(dimethylamino)phosphorane [(CH₃)₂N]₃P═NH in 125 ml ofanhydrous THF, cooled to −15° C. The mixture is left under constantstirring at this temperature for one hour (the diylide thus generatedmay be analyzed by phosphorus NMR, taking care to perform the withdrawalunder nitrogen). Under these conditions, 14 mmol (1 equivalent) ofbromine predried by means of an acidic wash (36% H₂SO₄) are added. Thereaction mixture is then stirred for 2 hours at a temperature of 0 to 5°C. 14 mmol of tris(dimethylamino)phosphine are finally added to thissolution. The mixture obtained is left under constant stirring for about12 hours (overnight).

[0261] The reaction mixture is filtered and the precipitate containingthe expected product is recovered. This product is taken up in a minimumamount of dichloromethane, to which are added a few drops of ethanoluntil the slight cloudiness has totally disappeared. The addition of alarge volume of ether allows the majority of the impurities to beremoved. The ether phase is then concentrated to dryness, taken up inether and left at low temperature overnight. The product in monobromoform is recovered in pure form by simple filtration and the solid isdried over P₂O₅ overnight in a desiccator.

[0262]³¹P NMR (ppm) (CDCl₃): 19.62 (s, 2P equivalent)

[0263]¹H NMR (ppm) (CDCl₃): 7.36-6.74 (t, 36H equivalent)

[0264]¹³C NMR (ppm) (CDCl₃): 36.50 (t, J² _(PC)=4.78 Hz) 2nd ordersystem

[0265] Mass: FAB⁺ M-Br⁻; 340 [NBA matrix]

[0266] Microanalysis EXP.: C: 34.29%; H: 8.64%; N: 23.00%; BR: 19.16%

[0267] THEO.: C: 34.26%; H: 8.51%; N: 23.31%; BR: 19.03%

EXAMPLE 11

[0268] Synthesis of [(Me₂N)₃-P═N═PBu₃]⁺Br⁻

[0269] 14 mmol of a solution of dibromine diluted beforehand in 10 ml ofdichloromethane at −5° C. are added dropwise to a solution of 14 mmol oftributylphosphine in 70 ml of anhydrous dichloromethane. The mixture isstirred for 1 hour at a temperature of 0 to −5° C. (in situ formation ofBu₃PBr₂).

[0270] After addition of 1.5 equivalents of triethylamine, 14 mmol ofiminotris(dimethylamino)phosphorane [(CH₃)₂N]₃P═NH in 14 ml of THF arethen added to the solution of dibromotributylphosphorane Bu₃PBr₂. Theresulting mixture is stirred overnight at room temperature.

[0271] The solution obtained is evaporated to dryness under reducedpressure. The residue recovered is taken up in ether and then filteredoff. The pasty, semi-solid product is taken up in dichloromethane andwashed with distilled water solution. The organic phase is dried overMgSO₄, filtered and then concentrated to dryness. The product is thensuspended in ether and left overnight at low temperature. The pastysolid contained in the ether phase is triturated in a bath of coldalcohol at −70° C. and the solution is filtered. The pure product isfinally dried in a desiccator over P₂O₅.

[0272]³¹P NMR (ppm) (CDCl₃): 29.62 (d, J² _(PP)=30.65 Hz); 23.18 (d, J²_(PP)=30.65 Hz)

[0273]¹H NMR (ppm) (CDCl₃): 2.6 (dd, 18H); 2 to 1.8 (m, ¹CH₂, 6H); 1.55to 1.3 (m, ²CH₂-³CH₂, 12H); 0.87 (t, CH₃, 9H) (ppm) (CDCl₃): 36.76 (d,J² _(PC)=4.47 Hz, MeN); 26.85 (dd,

[0274]¹³C NMR J¹ _(PC)=66.24 Hz, J³ _(PC)=1.49 Hz, CH₂): 23.36 (d, J²_(PC)=11.54 Hz, CH₂); 23.18 (s, CH₂CH₃); 13.20 (s, CH₃)

[0275] Mass: FAB⁺ M-Br⁻; 380 [NBA matrix]

[0276] Microanalysis EXP.: C: 45.66%; H: 9.73%; N: 11.70%; P:

[0277] 12.90% THEO.: C: 47.01%; H: 9.79%; N: 12.18%; P: 13.40%;

EXAMPLE 12

[0278] Synthesis of [(Me₂N)₃-P═N═PPh₃]⁺Br⁻

[0279] 14 mmol of a solution of dibromine diluted beforehand in 10 ml ofdichloromethane at −5° C. are added dropwise to a solution of 14 mmol oftriphenylphosphine in 70 ml of anhydrous dichloromethane. The mixture isstirred for 1 hour at a temperature of 0 to −5° C. (in situ formation ofPh₃PBr₂).

[0280] After addition of 1.5 equivalents of triethylamine, 14 mmol ofiminotris(dimethylamino)phosphorane [(CH₃)₂N]₃P═NH in 14 ml of THF arethen added to the solution of dibromotriphenylphosphorane Ph₃PBr₂.

[0281] After stirring overnight at room temperature, the reactionmixture is concentrated to dryness under reduced pressure. The solidresidue is taken up in ether and then filtered off. The recoveredprecipitate is dissolved in 150 ml of dichloromethane and washed twicewith 20 ml of distilled water. The organic phase is dried over MgSO₄ andthen evaporated to dryness. The white solid obtained is suspended in 50ml of ether and stirred for 30 minutes. The pure product is obtained bysimple filtration and dried in a desiccator overnight over P₂O₅.

[0282]³¹P NMR (ppm) (CH₂Cl₂): 26.48 (d, J² _(P-P)=37.3 Hz); 13.45 (d, J²_(P-P)=37.3 Hz)

[0283]¹H NMR (ppm) (CDCl₃) 2.52 (d, CH₃, 18H, J³ _(P-H)=10.35 Hz); 7.57to 7.44 (m, aromatic, 15H) ppm (CDCl₃): 152.72 (d, J⁴ _(PC)=3.01 Hz);150.92 (d, J³ _(PC)=

[0284]¹³C NMR 11.06 Hz) 148.68 (d, J² _(PC)=13.20 Hz); 147.21 (dd, J¹_(PC)=108.64 Hz, J³ _(PC)=2.54 Hz); 56.25 (d, J² _(PC)=4.52 Hz, MeN)

[0285] Mass: FAB⁺ M-Br⁻; 439 [NBA matrix]

[0286] Microanalysis EXP.: C: 45.66%; H: 9.73%; N: 11.70%; P: 12.90%THEO.: C: 47.01%; H: 9.79%; N: 12.18%; P: 13.40%;

EXAMPLE 13

[0287] Synthesis of Bu₃-P═N═PBu₃ ⁺Br⁻

[0288] This example shows the advantage of the synthetic technique,although the product is not among the preferred products.

[0289] Thus, 14 mmol of a solution of dibromine diluted beforehand in 10ml of dichloromethane at −5° C. are added dropwise to a solution of 14mmol of tributylphosphine in 70 ml of anhydrous dichloromethane. Themixture is stirred for 1 hour at a temperature of 0 to −5° C. (in situformation of Bu₃PBr₂).

[0290] After addition of 1.5 equivalents of triethylamine, 14 mmol ofBu₃P═NH (prepared by the action of 1 equivalent of BuLi on[Bu₃PNH₂]⁺Br⁻) in 14 ml of THF are then added to the solution ofdibromotributylphosphorane Bu₃PBr₂.

[0291] After reacting overnight, the reaction mixture is concentrated todryness and the residue recovered is taken up in 40 ml of THF. Thesolution is filtered and the organic phase containing the expected saltis evaporated to dryness. This salt is not entirely pure, since theresidue contains about 25% of the starting aminophosphonium salt that wedid not manage to separate out by recrystallization (on the basis of thephosphorus NMR). The precipitate is then heated at 160° C. for 5 hoursuntil the residual starting salt has disappeared. Recrystallization ofthe residue from CCl₄ thus allows the expected product to be obtained ina yield of 52%.

[0292]³¹P{¹H} NMR (CH₂Cl₂): 36.3 ppm (Bu₃PNPBu₃, Br) (57.2 ppm (Bu₃PNH₂,Br))

[0293]¹H NMR (CDCl₃): 0.93 ppm (t, 18H, CH₃): 1.45 ppm (m, 24H,CH₂-CH₂); 2.03 ppm (m, 12H, —CH₂—P) (CDCl₃): 13.66 ppm (s, CH₃): 23.88ppm (d, ²J_(P-C)=15.6

[0294]¹³C NMR Hz, CH₂); 24.02 ppm (d, ³J_(P-C)=4.5 Hz, CH₂); 27.15 ppm(d/d, ¹J_(P-C)=65.5 Hz, ³J_(P-C)≈0.4 Hz, CH₂)

[0295] Mass: FAB⁺ M-Br⁻; 418 [NBA matrix]

[0296] Microanalysis Awaiting

1. Use, as a catalyst for nucleophilic, advantageously aromatic,substitution, of a compound of general formula (I):

in which: R₁, R₂, R₃, R₄, R₅ and R₆, which may be identical ordifferent, are chosen from hydrocarbon-based radicals; the Pn, which areadvantageously the same, are chosen from the metalloid elements ofcolumn V from a period higher than that of nitrogen; Z is a metalloidelement from column V, which is advantageously different than Pn,preferably a nitrogen (N, P, As or Sb).
 2. The use as claimed in claim1, characterized in that the compounds of formula (I) are neutral. 3.The use as claimed in claim 1, characterized in that the compounds offormula (I) that are the easiest to use are cationic compounds and areadvantageously introduced in the form of a salt of formula (II):

in which X⁻ is a counterion chosen from anions and mixtures of anions,which anions and mixtures of anions are advantageously chosen frommonovalent anions.
 4. The use as claimed in claims 1 to 3, characterizedin that said hydrocarbon-based radicals R₁, R₂, R₃, R₄, R₅ and R₆ aregenerally chosen from: alkyls, optionally substituted aryls, amino andimino groups, advantageously in which the nitrogen linked to a Pn doesnot bear hydrogen, hydrocarbyloxy groups, a polymer arm.
 5. The use asclaimed in claims 1 to 4, characterized in that each of the radicals R₁,R₂, R₃, R₄, R₅ and R₆ contains not more than 20 carbon atoms.
 6. The useas claimed in claims 1 to 5, characterized in that the compound offormula (I) contains in total not more than 100 carbon atoms andpreferably not more than 60 carbon atoms.
 7. The use as claimed inclaims 1 to 6, characterized in that R₁, R₂ and R₃ are identical.
 8. Theuse as claimed in claims 1 to 7, characterized in that R₄, R₅ and R₆ areidentical.
 9. The use as claimed in claims 1 to 7, characterized in thatR₁, R₂, R₃, R₄, R₅ and R₆ are identical.
 10. The use as claimed inclaims 1 to 9, characterized in that at least 3, advantageously at least4, preferably at least 5 and more preferably all of the radicals R₁, R₂,R₃, R₄, R₅ and R₆ are linked to the Pn via aromatic carbon atoms and/ora nitrogen atom of a peralkylated amine or imine function.
 11. The useas claimed in claims 3 to 10, characterized in that the counterions X⁻are chosen from anions and mixtures of anions that are sparinglynucleophilic.
 12. A composition that is useful for nucleophilicsubstitutions, characterized in that it comprises a polar aproticsolvent, a nucleophilic agent, which is advantageously anionic, acompound of formula (I) as claimed in claims 1 to 11, The molar ratiobetween the catalyst and the nucleophilic agent used in the reactionbeing not less than 0.1%, advantageously 0.5%, preferably 1% and morepreferably 0.5%.
 13. The composition as claimed in claim 12,characterized in that said nucleophile is chosen from halides,advantageously a fluoride.
 14. A nucleophilic substitution process,characterized in that a substrate of general formula (III):Ar-(Ξ)  (III)in which Ar is an aromatic radical in which the nucleusbearing Ξ is electron-poor either because it comprises at least onehetero atom in its ring, or because the sum of the σ_(p) of itssubstituents, besides the Ξ, is at least equal to 0.2, advantageously0.4 and preferably 0.5; and in which Ξ is a leaving group,advantageously in the form of an anion Ξ⁻, is placed in contact with acomposition as claimed in claims 12 and
 13. 15. The process as claimedin claim 14, characterized in that Ar bears at least 1 leaving groupother than Ξ.
 16. A cationic compound that is useful as a nucleophilicsubstitution catalyst, of general formula I:

in which: R₁, R₂, R₃, R₄, R₅ and R₆, which may be identical ordifferent, are chosen from hydrocarbon-based radicals; the Pn, which areadvantageously the same, are chosen from the metalloid elements ofcolumn V from a period higher than that of nitrogen; Z is a metalloidelement from column V, which is advantageously different than Pn,preferably a nitrogen (N, P, As or Sb), characterized in that not morethan two of the radicals R₁ to R₃ and/or not more than two of theradicals R₄ to R₆ are alkyls and in that it contains more than 12 carbonatoms.
 17. A process for synthesizing a compound of general formula I

in which: R₁, R₂, R₃, R₄, R₅ and R₆, which may be identical ordifferent, are chosen from hydrocarbon-based radicals; the Pn, which areadvantageously the same, are chosen from the metalloid elements ofcolumn V from a period higher than that of nitrogen; Z is a metalloidelement from column V, which is advantageously different than Pn,preferably a nitrogen (N, P, As or Sb); characterized in that itcomprises a step in which: a trivalent Pn compound; an iminoid offormula (R₁) (R₂) (R₃) Pn═ZM in which m represents a hydrogen or,advantageously, a cation giving a well-dissociated salt, chosenespecially from quaternary ammoniums, quaternary phosphoniums andadvantageously from alkali metals, preferably lithium; and whereappropriate, a reagent capable of giving a positive halogen withoutreleasing water, are successively or simultaneously reacted.
 18. Theprocess as claimed in claim 17, characterized in that said reagentcapable of giving a positive halogen without releasing water is amolecular halogen, advantageously bromine.
 19. The process as claimed inclaims 17 and 18, characterized in that said iminoid is subjected to theaction of a halogen (X₂) before or during the placing in contact withthe trivalent compound of formula P(R₄) (R₅) (R₆) to give one of thefollowing reaction sequences:


20. The process as claimed in claims 17 and 18, characterized in thatsaid trivalent Pn compound is a phosphine of formula P(R₄) (R₅) (R₆) andis subjected to the action of a halogen, advantageously bromine (Br₂),to form, at least transiently, a halophosphonium halide of formula:

before or during the placing in contact with the iminoid oradvantageously a salt thereof and in which R₁, R₂, R₃, R₄, R₅ and R₆ aredefined above.
 21. The process as claimed in claim 17, characterized inthat said trivalent Pn derivative is halogenated and in that no reagentcapable of giving a positive halogen without releasing water is added,so as to perform one of the following reactions: